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Functionalized High Mannose‐Specific Lectins for the Discovery of Type I Mannosidase Inhibitors
Author(s) -
Kurhade Suresh E.,
Weiner Jack D.,
Gao Fei Philip,
Farrell Mark P.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202101249
Subject(s) - mannosidase , mannose , glycan , lectin , glycosylation , biochemistry , c type lectin , chemistry , biology , glycoprotein
An engineered cyanovirin‐N homologue that exhibits specificity for high mannose N‐glycans has been constructed to aid type I α 1,2‐mannosidase inhibitor discovery and development. Engineering the lectins C‐terminus permitted facile functionalization with fluorophores via a sortase and click strategy. The resulting lectin constructs exhibit specificity for cells presenting high mannose N‐glycans. Importantly, these lectin constructs can also be applied to specifically assess changes in cell surface glycosylation induced by type I mannosidase inhibitors. Testing the utility of these lectin constructs led to the discovery of type I mannosidase inhibitors with nanomolar potency. Cumulatively, these findings reveal the specificity and utility of the functionalized cyanovirin‐N homologue constructs, and highlight their potential in analytical contexts that require high mannose‐specific lectins.